Involvement of lipid peroxidation, oncogene expression and induction of apoptosis in the antitumorous activity of feric-sorbitol-citrate (CROSBI ID 89282)
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Poljak-Blaži, Marija ; Kralj, Marijeta ; Popović Hadžija, Marijana ; Žarković, Neven ; Žarković, Kamelija ; Waeg, Georg
engleski
Involvement of lipid peroxidation, oncogene expression and induction of apoptosis in the antitumorous activity of feric-sorbitol-citrate
We described before that iron-containing, anti-anemic drug, ferric-sorbitol-citrate complex (FSC) inhibited proliferation of various murine cancer cells in vitro and caused tumour regression in vivo, but did not affect proliferation of the non-malignant cells. The aim of this study was to evaulate further the anticancer activity mechanism of FCS using human colon cancer cell line CaCo2. After treatment with FSC for 72 hours impaired proliferative ability and viability of CaCo2 cells as observed. Growth modification caused by FSC involved diminished expression of Bcl.2, and over-expression of mp53 proto-oncogenes, accompanied by increased incidence of apoptosis. Immunostaining the cells applying monoclonal antibodies for lipid peroxidation prodict 4-hydroxynonenal (HNE) showed that FSC � iron increased intracelular HNE, but did not induce severe HNE-mediated oxidative stress. Thus, antitumours mechanism of FSC involves modulation of oncogene expression and induction of apotosis apparently not triggered by lipid peroxidation-mediated oxidative stress, although FSC might restore endogenous HNE production in the CaCo2 cells to level resembling physiological for various non-malignant cells and tissues. Higher dose of FSC increased also number of intracellular ferritin positive CaCo2 cells.
ferric sorbitol citrate; iron; ferritin; growth modulation; oncogenes
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Povezanost rada
Kemija, Temeljne medicinske znanosti, Biologija